Ando R, Kawamura M, Chiba N
Research Laboratory, Pharmaceuticals Research Division, Mitsubishi Pharma Corporation, 1000 Kamoshida-cho, Aoba-ku, Yokohama 227-0033, Japan.
J Med Chem. 2001 Dec 6;44(25):4468-74. doi: 10.1021/jm010307o.
After chemical modification preceded by the random screening of our chemical library, a novel class of selective anti-Helicobacter pylori agents was generated. Consequently, the 3-(arylacetylamino)-N-methylbenzamides, which were quite easy to prepare, showed potent inhibitory activity against Helicobacter pylori but exhibited no inhibitory activity against other sorts of bacteria and fungi, e.g., Staphylococcus aureus, Bacillus subtilis, Escherichia coli, Pseudomonas aeruginosa, Bacteroides fragilis, and Candida albicans. These compounds showed potent anti-H. pylori activity under acidic conditions, whereas amoxicillin and clarithromycin decreased activity. The 3-(3-arylpropionylamino)-N-methylbenzamides, 3-(aryloxyacetylamino)-N-methylbenzamides, and (3-methylcarbamoylphenyl)carbamic acid 1-arylmethyl esters also exhibited potent anti-H. pylori activity. Finally, we selected 7n (BAS-118) as a candidate compound for further evaluation.
在对我们的化学文库进行随机筛选后进行化学修饰，生成了一类新型的选择性抗幽门螺杆菌药物。因此，制备相当容易的3-(芳基乙酰氨基)-N-甲基苯甲酰胺对幽门螺杆菌显示出强效抑制活性，但对其他种类的细菌和真菌，如金黄色葡萄球菌、枯草芽孢杆菌、大肠杆菌、铜绿假单胞菌、脆弱拟杆菌和白色念珠菌没有抑制活性。这些化合物在酸性条件下显示出强效抗幽门螺杆菌活性，而阿莫西林和克拉霉素的活性则降低。3-(3-芳基丙酰氨基)-N-甲基苯甲酰胺、3-(芳氧基乙酰氨基)-N-甲基苯甲酰胺和(3-甲基氨基甲酰基苯基)氨基甲酸1-芳基甲酯也表现出强效抗幽门螺杆菌活性。最后，我们选择7n（BAS-118）作为进一步评估的候选化合物。
